Abnormally high levels of immune complexes (IC) were found in 20% to 25% of the sera from 53 patients with disseminated (Stage III or IV) malignant melanoma (MM) and in 47% of the sera from 17 children with disseminated neuroblastoma (NBL). In MM, IC measured by the C1q binding test were helpful in estimating prognosis, whereas IC detected by the Raji cell assay were not. In NBL, the Raji cell assay detected IC more frequently than the C1q binding test, but neither was useful in estimating prognosis. Surprisingly, we found that serum IC levels correlated with the level of antibodies (Abs) to bovine serum albumin (BSA). Sera with high IC levels and low antiBSA levels contained "hidden" antibodies to BSA, evident when the IC were acid dissociated. One human NBL tumor line, maintained in serum free medium, was found to release proteins that crossreact with BSA. We postulate that antigens released by some NBL may be partly responsible for the high levels of anti-BSA found in the sera of certain patients; however, BSA-containing antigens from food may compete with tumor cell products for available circulating Abs to BSA with the result that serum IC fluctuate out of synchrony with changes in tumor burden. In contrast, in the MM patients, sera that lacked IC contained Abs that were cytotoxic for certain human MM cell lines; these Abs were not evident in sera that contained IC until the IC were dissociated. Methods have been developed to identify and purify to homogeneity certain of the antigens on human MM that are recognized by Abs in patient sera. Solid-phase radioimmunoassays have been developed to quantitate the Abs to these tumor cell products in order to determine which are best for monitoring patients with MM. In other studies, blocking antibodies, putatively anti-idiotypes, have been demonstrated to be one of the agents that are coupled to the antitumor cell Abs in the serum. Future experiments will address the hypotheses that excessive synthesis of these blocking Abs is a characteristic of patients who have rapidly progressive disease and that complexes of antitumor Abs and blocking Abs are important components of the IC in the sera of patients with MM, and possibly with other tumors as well.